We have found that both reperfusion injury and thermal burns are critically dependent on a single natural IgM specificity, Without the IgM, injury is signficantly diminished. We have now identified potential antigens to which the IgM and used short peptide fragments to inhibit the evolution of injury in mice that respond normally to injury otherwise. This proposal seeks to determine whether humans manifest a similar pathbiology that is dependent on a limited number of natural antibody specificities. In addition, the proposal seeks to determine whether there are more severe conditions of injury in which these mechanisms no longer apply, and why.